CN117463417A

CN117463417A - System and apparatus for microfluidic cartridges

Info

Publication number: CN117463417A
Application number: CN202311503337.XA
Authority: CN
Inventors: A·克莱兰; J-L·弗雷坎; P·迈因霍尔德; F·蒙松
Original assignee: Spectradyne LLC
Current assignee: Spectradyne LLC
Priority date: 2015-11-25
Filing date: 2016-11-22
Publication date: 2024-01-30
Also published as: EP3380846A1; US20180345285A1; WO2017091625A1; JP7185525B2; EP3380846A4; CN108700601A; JP2019500594A

Abstract

The present application relates to systems and devices for microfluidic cartridges. Various embodiments of the present disclosure include microfluidic cartridges comprising a molded polymer bonded to a planar surface, wherein the molded polymer comprises one or more openings for connecting to a volume of fluid. Also provided are methods of making microfluidic cartridges that include placing patterned microfabricated chips into a mold and filling the mold with a liquid or other shape conforming form of material. Further disclosed herein are methods of analyzing a particle sample by using a microfluidic sample.

Description

System and apparatus for microfluidic cartridges

The present application is a divisional application of chinese patent application No. 201680079940.1 (corresponding international patent application No. PCT/US 2016/063121) entitled "system and device for microfluidic cartridges" with priority date of 11/25/2015.

Technical Field

The present invention relates generally to nanotechnology, and more particularly to systems and devices for microfluidic instruments and analysis.

Background

All publications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The following description includes information useful for understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.

Applications for synthesizing nanoparticles include cosmetics, photovoltaic devices, and nanomedicines. Naturally occurring microparticles and nanoparticles mediate important physiological processes, and lethal viruses of about 50-150 nm in diameter kill millions of people each year. However, practical development and use of nanoparticles is greatly limited by the lack of practical tools capable of detecting and characterizing particles in this size range. Accordingly, there is a need in the art for novel and efficient methods and related apparatus for nanoparticle analysis.

Disclosure of Invention

Embodiments of the present disclosure include a microfluidic cartridge (microfluidic cartridge) comprising: a molded polymer bonded to the planar surface, wherein the molded polymer comprises one or more openings for connecting to the fluid volume. In one embodiment, the microfluidic cartridge further comprises a microfabricated chip. In one embodiment, the planar surface further comprises one or more electrodes. In one embodiment, one or more connections provide a gaseous and/or fluid connection. In one embodiment, the molding polymer is an organic molding polymer. In one embodiment, the planar surface comprises a glass surface. In one embodiment, the one or more openings are adapted to introduce fluid into the cartridge without contacting the connection instrument. In one embodiment, the microfluidic cartridge further comprises microfluidic cartridge regions having different open fluid volumes. In one embodiment, the cartridge allows multiple uses, using the same or different samples. In one embodiment, the fluid volume comprises a microfluidic volume. In one embodiment, a microfluidic cartridge is described by figures 1-5 herein.

Embodiments of the present disclosure also include a method of making a microfluidic cartridge, the method comprising: placing the patterned microfabricated chip into a mold; and filling the mold with a liquid or other shape conforming form of material. In one embodiment, the patterned microfabricated chip is patterned using advanced photolithographic techniques. In one embodiment, the material is an organic polymer. In one embodiment, the material is thermally cured and/or time cured. In one embodiment, the patterned microfabricated chip is made of a silicon substrate. In one embodiment, the mold is described by fig. 6 herein.

Embodiments of the present disclosure also include a method of analyzing a sample comprising particles, the method comprising: providing a microfluidic cartridge comprising a molded polymer bonded to a planar surface and analyzing a sample using the microfluidic cartridge, wherein the molded polymer comprises one or more openings for connection to a fluid volume. In one embodiment, the sample comprises microparticles and/or nanoparticles. In one embodiment, the sample is a biological sample. In one embodiment, the microfluidic cartridge further comprises a patterned metal electrode. In one embodiment, the patterned metal electrode is in contact with the microfluidic volume in some portion of the cartridge, and the patterned metal electrode is not in contact with the microfluidic volume in the remainder of the cartridge.

Drawings

Exemplary embodiments are shown in the referenced figures. The embodiments and figures disclosed herein are to be regarded as illustrative rather than restrictive.

Fig. 1 depicts an example of an electrode configuration according to embodiments herein. The outline of the molded polymer 102 and the chip 104 is shown. In one embodiment, the chip 104 is made of glass.

Fig. 2 depicts a transitional bridging detail (crossover detai l) according to embodiments herein. In one embodiment, contact electrodes 110 and electrode transition crossover details 108 in a microfluidic cartridge are illustrated. The edges of the covered molded polymer 102 are shown by dashed lines.

Fig. 3 depicts fuse details showing contact of electrode 110 with fuse 112, according to embodiments herein.

Fig. 4 depicts an example of a cartridge according to embodiments herein. (a) a top view of the cartridge; and (B) a side view of the cassette. Fig. 4 (a) shows the positions of the sealing ring 116, the reservoir 118, the port 120 and the electrode 110. Fig. 4 (b) shows the positions of the sealing ring 116 and the reservoir 118.

Fig. 5 depicts an example of a cartridge according to embodiments herein. The figure shows a number of examples of possible box thickness dimensions and examples. In this embodiment, a buffer on the fluid retarder side 124, a buffer on the nano-constriction side 126, a fluid input/output port 120, an analyte input port 134, an analyte-waste port 136, a main flow 132 of fluid, a particle detection flow 138, a nano-constriction 122 (nanocons tr ict ion), and a fluid retarder 130 (res is tor) are shown.

Fig. 6 depicts an example of a mold 140, showing a machined insert 142, a microfabricated insert 144, an insert backing 146, an insert backing spring 148, a syringe 150, and a post 152, according to embodiments herein. In one embodiment, the mold may be used in conjunction with the various microfluidic devices and instruments described herein.

Other features and advantages of the invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, illustrating by way of example various embodiments of the invention.

Detailed Description

All documents cited herein are incorporated by reference in their entirety as if fully set forth. Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The following documents provide those skilled in the art with a general guidance for many of the terms used in this application: hornyak, et al, introduct ion to Nanosc ience and Nanotechnology, CRC Pres (2008); s ingleton et al, dict ionary of Microbiology and Molecular Biology, 3rd ed., J.wi ley & Sons (New York, N.Y. 2001); march, advanced Organic Chemi s try React ions, mechani sms and Structure th ed., J.wi ley & Sons (New York, NY 2013); and Sambrook and Rus sel, molecular Cloning: A Laboratory Manua l4th ed., cold Spr ing Harbor Laboratory Press (Cold Spr ing Harbor, NY 2012). Those skilled in the art will recognize many methods and materials similar or equivalent to those described herein that can be used in the practice of the present invention. Indeed, the invention is in no way limited to the methods and materials described.

As disclosed herein, the inventors have developed a microfluidic cartridge comprising a molded polymer bonded to a planar surface, wherein the molded polymer comprises one or more openings for connection to a fluid volume. The profile of the molded polymer 102 is shown in fig. 1. In one embodiment, the microfluidic cartridge further comprises a microfabricated chip 104. In one embodiment, the planar surface further includes one or more electrodes 110. In one embodiment, one or more connections provide a gaseous and/or fluid connection. In one embodiment, the molding polymer is an organic molding polymer. In one embodiment, the planar surface is glass. In one embodiment, the one or more openings are adapted to introduce fluid into the cartridge without contacting the connection instrument. In one embodiment, the microfluidic cartridge further comprises microfluidic cartridge regions having different open fluid volumes. In one embodiment, the cartridge allows multiple uses, using the same or different samples. In one embodiment, the fluid volume comprises a microfluidic volume. In one embodiment, a microfluidic cartridge is described by figures 1-5 herein.

In one embodiment, disclosed herein is a method of making a microfluidic cartridge comprising: placing the patterned microfabricated chip 104 into a mold; and filling the mold with a liquid or other shape conforming form of material. In one embodiment, advanced photolithography techniques are used to pattern the patterned microfabricated chip 104. In one embodiment, the material is an organic polymer. In one embodiment, the material is thermally cured and/or time cured. In one embodiment, patterned micro-fabricated chip 104 is made of a silicon substrate. In one embodiment, the mold is described by fig. 6 herein.

In one embodiment, disclosed herein is a method of analyzing a sample comprising particles, comprising: providing a microfluidic cartridge comprising a molded polymer bonded to a planar surface and analyzing a sample using the microfluidic cartridge, wherein the molded polymer comprises one or more openings for connection to a fluid volume. In one embodiment, the sample comprises microparticles and/or nanoparticles. In one embodiment, the sample is a biological sample. In one embodiment, the microfluidic cartridge further comprises a patterned metal electrode 110. In one embodiment, the patterned metal electrode 110 is in contact with the microfluidic volume in some portion of the cartridge, and the patterned metal electrode 110 is not in contact with the microfluidic volume in the rest of the cartridge.

In one embodiment, FIG. 1 shows the profile of molded polymer 102 and chip 104. In one embodiment, fig. 2 illustrates contact electrodes 110 and electrode transition crossover details 108 in a microfluidic cartridge as disclosed herein. The edges of the covered molded polymer 102 are shown by dashed lines. In one embodiment, fig. 3 discloses the contact of electrode 110 with fuse 112. Fig. 4 (a) shows another embodiment of the cartridge disclosed herein. In this embodiment, the positions of seal ring 116, reservoir 118, port 120, and electrode 110 are disclosed. Fig. 4 (b) shows another embodiment of the cartridge, which discloses the positions of the sealing ring 116 and the reservoir 118. Fig. 5 provides an illustrative example of a possible box thickness. In this embodiment, a buffer on the fluid retarder side 124 and a buffer on the nano-constriction side 126 are shown. Also shown is fluid input/output port 120, as well as analyte input port 134 and analyte-waste port 136. The main flow 132 of fluid, particle detection flow 138, nano constriction 122, and fluid retarder 130 for this embodiment are shown in fig. 5. Fig. 5 further illustrates various examples of possible box thickness dimensions and examples. Fig. 6 shows a microfluidic cartridge die 140, a machined insert 142, a microfabricated insert 144, an insert backing 146, an insert backing spring 148, a syringe 150, and a post 152.

In various embodiments herein, the present disclosure provides methods of preparing a microfluidic cartridge by using a mold 140. For example, in one embodiment, the present disclosure provides a method of molding a microfluidic device using the microfabricated insert 144. In one embodiment, the present disclosure provides a method of manufacturing a microfluidic cartridge using, for example, single or multiple parts of an organic polymer or other material that is thermally and/or time cured. The mold 140 is filled with a material in liquid form, and in this embodiment, the mold 140 includes, for example, a microfabricated chip 104, which itself is patterned using advanced photolithographic techniques. In another embodiment, the chip 104 may be made of a silicon substrate or other material compatible with the photolithographic technique. In another embodiment, the chip 104 is patterned independently of the metal mold 140. In another embodiment, after patterning of the chip 104 is completed, the chip 104 is placed and sealed into a mold 140 so that its features can be replicated in the cured organic polymer or other material. Thus, the cured organic polymer or other material, for example, accurately replicates all of the features in the mold 140 and embedded microfabricated chip 104.

In another embodiment, the present disclosure provides molded openings for gas and/or fluid connection to microfluidic volumes. For example, in one embodiment, the machining die 140 for forming an organic polymer includes one or more machined or otherwise patterned posts (pos) for forming openings or ports 120 in the cured polymer, allowing for the introduction of fluids or gases from an instrument into a microfluidic volume that is simultaneously patterned in the polymer. In another embodiment, the openings or ports 120 lead from one surface of the cured polymer block (block) to an opposing surface, which is patterned, for example, by the microfabricated chip 104 described in example 1 herein. In another embodiment, the openings or ports 120 are smooth cylinders that pass completely through the polymer. In another embodiment, the openings or ports 120 may have other shapes than cylinders. In another embodiment, the openings or ports 120 may pass through other surfaces of the organic polymer in the other direction.

In another embodiment, the present disclosure provides a molded opening for introducing a fluid without contacting an instrument. In one embodiment, for example, the cartridge includes one or more volumes into which fluid may be placed prior to loading the cartridge into the instrument, allowing, for example, the fluid to be analyzed to be introduced so that the fluid does not contact the instrument, avoiding contamination of the fluid and instrument, and minimizing the volume of fluid required for analysis.

In another embodiment, the present disclosure includes a microfluidic channel design. For example, in one embodiment, as shown in fig. 5, a microfabricated chip 104 for patterning microfluidic circuits may include patterns with different heights in different portions of the design in this embodiment, thereby creating regions of different open fluid volumes in the microfluidic cartridge. This can be used, for example, to greatly reduce the flow resistance, which serves to make the microfluidic volumes easier to fill and to make it easier to precisely control the pressure in these volumes. In another embodiment, the pattern area may be made larger when equally easy filling and pressure control is required. In another embodiment, the portion of the microfluidic circuit in which the fluid to be analyzed is introduced may be connected to the "waste" port 136 by a low flow resistance connection, allowing easy pressure control and filling of these volumes, independent of the volumes contacted by the fluid retarder 130 or the nanoshrinking section 122 alone. In another embodiment, the volume contacted by the fluid retarder 130 or the nano-constriction 122 may be made of a pattern of large area and/or large height to reduce flow resistance and make filling easier.

In another embodiment, relatively large volumes of fluid are moved into, through, or out of the cassette via readily filled volumes produced in connection with the embodiments further described herein, without having to move relatively large volumes of fluid through sections having high flow resistance.

In another embodiment, the fluid network is designed such that the fluid to be analyzed passes through the analysis zone before contacting any other fluid, so that it is not diluted or contaminated prior to analysis.

In another embodiment, the present disclosure provides an electrode design in a microfluidic cartridge. In one embodiment, the microfluidic cartridge is fabricated by bonding a molded organic polymer or other material to a planar surface made of glass or other material. In another embodiment, the planar surface includes one or more patterned metal electrodes 110 for applying or sensing a voltage or current, as shown in fig. 1. For example, the electrodes 110 in some parts of the cartridge are encapsulated in microfluidic volumes and are not in contact with these volumes in other areas. In another embodiment, in the transition between the microfluidic volumes and outside these volumes, the electrodes 110 may be divided into smaller width electrodes 110 to improve the sealing of the molding material to the planar surface. This provides a more reliable seal between, for example, the molding material and the planar surface, which sometimes does not seal well to the metal electrode 110 and thus allows fluid to leak from the microfluidic volume. In another embodiment, the width and number of these smaller electrode leads may be optimized to provide an optimal seal while minimizing any detrimental electrical problems associated with this feature. In another embodiment, the microfluidic cartridge is as described in figures 1 and 2 herein.

In another embodiment, the present disclosure provides a method of determining a first use of a cartridge. For example, in one embodiment, the cartridge is manufactured in a manner that allows for multiple uses of a single cartridge, possibly with the same or different analyte samples. However, the first use of the cartridge is the only use, e.g., in which case no cross-contamination between analytes occurs, no pre-cleaning is required, the cartridge filter is still clean, etc. Thus, in one embodiment, the inventors have implemented a method of first use of a cartridge. For example, the method may involve including a fuse 112 in the patterned metal on the glass portion of the cartridge that may be optionally opened (changing it from a low resistance to a very high resistance) with an electrical signal from the instrument. In another embodiment, the fuses 112 may also be tested with an electrical signal from an instrument to verify whether a particular cartridge has a broken fuse 112, thereby verifying whether the cartridge has been previously used. In another embodiment, the software in the instrument may then interact with the user of the instrument in different ways depending on the results of the test. In another embodiment, additional fuses 112 on the cartridge electrode 110 and corresponding wiring and circuitry in the instrument allow for a second, third, etc. use of the cartridge to be similarly detected. In another embodiment, for example, a microfluidic cartridge is as described in fig. 3 herein.

Various embodiments of the present invention describe microfluidic cartridges and devices, and methods of making and using the same, that can be used to analyze and/or modify biological samples, including samples containing one or more nanoparticles. It will be readily apparent to those of skill in the art that any method involving nanoparticle or biological sample analysis may be used in conjunction with the various embodiments described herein, and that the present disclosure may also include methods of diagnosis, prognosis and/or treatment of a disease or disorder in a subject. For example, in one embodiment, the present disclosure provides a method of diagnosing cancer in a subject by obtaining a sample from the subject and then using a microfluidic cartridge comprising a molded polymer bound to a planar surface (wherein the molded polymer comprises one or more openings for connecting to a microfluidic volume) to analyze the biological sample to determine the presence or absence of one or more biomarkers associated with a susceptibility to cancer, and diagnosing a susceptibility to cancer based on the presence of the one or more biomarkers.

The various methods and techniques described above provide many ways to implement the invention. Of course, it is to be understood that not necessarily all such objects or advantages may be achieved in accordance with any particular embodiment described herein. Thus, for example, those skilled in the art will recognize that the methods may be performed in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other objects or advantages as may be taught or suggested herein. Various advantageous and disadvantageous alternatives are mentioned herein. It should be understood that some preferred embodiments specifically include one, another, or several advantageous features, while others explicitly do not include one, another, or several disadvantageous features, while still others explicitly mitigate existing disadvantageous features by including one, another, or several advantageous features.

Furthermore, the skilled artisan will recognize the applicability of the various features from different embodiments. Similarly, one of ordinary skill in the art may mix and match the various elements, features, and steps discussed above, as well as other known equivalents for each such element, feature, or step, in order to perform methods according to the principles described herein. Among the various elements, features and steps, some will be specifically included in different embodiments and others will be specifically excluded.

Although the invention has been disclosed in the context of certain embodiments and examples, it will be understood by those skilled in the art that embodiments of the invention extend beyond the specifically disclosed embodiments to other alternative embodiments and/or uses and modifications and equivalents thereof.

Many variations and alternative elements have been disclosed in the embodiments of the invention. Further variations and alternatives will be apparent to those skilled in the art. In these variations, the component modules selected for use in the compositions of the invention are not limited, as well as diseases and other clinical conditions for which diagnosis, prognosis or treatment may be employed. Various embodiments of the invention may specifically include or exclude any of these variations or elements.

In some embodiments, the numbers expressing quantities of ingredients, properties such as concentration, reaction conditions, and so forth used to describe and claim certain embodiments of the present invention are to be understood as being modified in some instances by the term "about". Accordingly, in some embodiments, the numerical parameters set forth in the written specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the particular embodiment. In some embodiments, numerical parameters should be construed in light of the numerical values reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. The numerical values presented in some embodiments of the present invention may contain certain errors necessarily caused by the standard deviation present in their respective test measurements.

In some embodiments, the use of the terms "a" and "an" and "the" and similar referents in the context of describing particular embodiments of the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated, each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided with respect to certain embodiments herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

The grouping of alternative elements or embodiments of the invention disclosed herein should not be construed as limiting. Each group member may be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more group members may be included in or deleted from the group for convenience and/or patentability reasons. When any such inclusion or deletion occurs, the specification is considered herein to contain the modified group so as to satisfy the written description of all markush groups used in the appended claims.

Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. It is contemplated that the skilled artisan will be able to utilize these variations as appropriate and be able to practice the invention in a manner other than as specifically described herein. Accordingly, many embodiments of the invention include all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Furthermore, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

In addition, numerous references are made throughout the specification to patents and printed publications. Each of the references and printed publications cited above are incorporated by reference in their entirety.

Finally, it is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the invention. Other modifications that may be utilized may be within the scope of the present invention. Thus, by way of example, and not limitation, alternative configurations of the present invention may be utilized in accordance with the teachings herein. Accordingly, embodiments of the invention are not limited to those precisely shown and described.

Examples

The following examples are provided to better illustrate the claimed invention and should not be construed as limiting the scope of the invention. To the extent that specific materials are mentioned, they are for illustrative purposes only and are not intended to limit the invention. Equivalent means or reactants can be developed by those skilled in the art without the need for the creation of the capability and without departing from the scope of the invention.

Example 1

Molding microfluidic devices using microfabricated inserts 144

Microfluidic cartridges are fabricated using single or multicomponent organic polymers or other thermally and/or time curable materials. The mold 140 is filled with a material in liquid form, and in this embodiment, the mold 140 includes a microfabricated chip 104, which itself is patterned using advanced photolithographic techniques. The chip 104 may be made of a silicon substrate or other material compatible with the photolithographic technique and patterned separately from the metal mold. After patterning of the chip 104 is completed, the chip 104 in this embodiment is placed and sealed into a mold 140 so that its features can be replicated in the cured organic polymer or other material. Thus, the cured organic polymer or other material accurately replicates all of the features in the mold and embedded microfabricated chip 104.

Example 2

Molded opening for gas and fluid connection to microfluidic volumes

The machining die used to form the organic polymer in this embodiment includes one or more machined or otherwise patterned pillars 152 that are used to form openings or ports 120 in the cured polymer, allowing the introduction of fluids or gases from the instrument into the simultaneously patterned microfluidic volumes in the polymer. In one embodiment, these openings or ports 120 lead from one surface of the cured polymer block to an opposing surface, such as patterned by the microfabricated chip 104 described in example 1 of the present invention. In one embodiment, the openings or ports 120 are smooth cylinders that pass completely through the polymer. In another embodiment, the openings or ports 120 may have other shapes than cylinders. In another embodiment, these openings or ports 120 may pass through other surfaces of the organic polymer in the other direction.

Example 3

Molded opening for introducing fluid without contacting the instrument

The cartridge includes one or more volumes into which fluid may be placed prior to loading the cartridge into the instrument, allowing, for example, the fluid to be analyzed to be introduced so that the fluid does not contact the instrument, avoiding contamination of the fluid and instrument, and minimizing the volume of fluid required for analysis.

Example 4

Microfluidic channel design

The microfabricated chip 104 used to pattern the microfluidic circuit in this embodiment may include patterns with different heights in different portions of the design, creating regions of different open fluid volumes in the microfluidic cartridge. This can be used to greatly reduce the flow resistance, which serves to make the microfluidic volumes easier to fill and to make it easier to precisely control the pressure in these volumes. In the same or another embodiment, the pattern area may be made larger when equally easy filling and pressure control is required. In the same or another embodiment, the portion of the microfluidic circuit in which the fluid to be analyzed is introduced may be connected to the "waste" port 136 by a low flow resistance connection, allowing easy pressure control and filling of these volumes, independent of the volumes contacted only by the fluid retarder 130 or the nanoshrinking section 122. In this or another embodiment, the volume contacted by the fluid retarder 130 or the nano-constriction 122 may be made of a pattern of large area and/or large height to reduce the flow resistance and make filling easier.

In one embodiment, a relatively large volume of fluid is moved into, through, or out of the cassette by an easily filled volume created, for example, by the described method, without having to move the relatively large volume of fluid through a section having a high flow resistance.

In one embodiment, the fluid network is designed such that the fluid to be analyzed passes through the analysis area before contacting any other fluid, so that it is not diluted or contaminated prior to analysis.

Example 5

Electrode design in microfluidic cartridges

In one embodiment, the microfluidic cartridge is fabricated by bonding a molded organic polymer or other material to a planar surface made of glass or other material. In this embodiment, the planar surface includes one or more patterned metal electrodes 110 for applying or sensing a voltage or current. The electrodes 110 in some parts of the cartridge are encapsulated in microfluidic volumes and are not in contact with these volumes in other areas. In the transition between the microfluidic volumes and the outside of these volumes, the electrode 110 may be divided into smaller width electrodes 110 to improve the sealing of the molding material to the planar surface. This provides a more reliable seal between the molding material and the planar surface, which sometimes does not seal well to the metal electrode 110 and thus allows fluid to leak from the microfluidic volume. The width and number of these smaller electrode leads can be optimized to provide an optimal seal while minimizing any detrimental electrical problems associated with this feature. For example as described in fig. 1 and 2 herein.

Example 6

Method for determining first use of a cartridge

The cartridge is manufactured in a manner that allows for multiple uses of a single cartridge, possibly with the same or different analyte samples. However, the first use of the cartridge is the only use, e.g., cross-contamination between analytes does not occur, pre-cleaning is not required, the cartridge filter is still clean, etc. Thus, in one embodiment, the inventors have implemented a method of first use of a cartridge. The method involves including a fuse 112 in the patterned metal on the glass portion of the cartridge that can be optionally opened (from low to very high resistance) with an electrical signal from the instrument. The fuses 112 may also be tested with electrical signals from the instrument to verify whether a particular cartridge has a broken fuse 112, thereby verifying that the cartridge has been previously used. The software in the instrument can then interact with the user of the instrument in different ways depending on the results of the test. In another embodiment, additional fuses 112 on the cartridge electrode 110 and corresponding wiring and circuitry in the instrument allow for a second, third, etc. use of the cartridge to be similarly detected. An example of such a fuse 112 is described in fig. 3 herein.

Various embodiments of the present invention are described above in the detailed description. While the description directly describes the above embodiments, it should be understood that modifications and/or variations to the specific embodiments shown and described herein will occur to those skilled in the art. Any such modifications or variations that fall within the scope of this specification are intended to be included therein. Unless specifically stated otherwise, it is the intention of the inventors that words and phrases in the specification and claims be given the ordinary and accustomed meaning known to those of ordinary skill in the applicable arts.

The foregoing description of various embodiments of the invention that applicant has appreciated at the time of filing this application has been presented and is intended for purposes of illustration and description. The present description is not intended to be exhaustive or to limit the invention to the precise form disclosed, and many modifications and variations are possible in light of the above teaching. The described embodiments are provided to explain the principles of the invention and its practical application and to enable others skilled in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated. Therefore, it is intended that the invention not be limited to the particular embodiments disclosed for carrying out this invention.

While particular embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that, based upon the teachings herein, changes and modifications may be made without departing from this invention and its broader aspects and, therefore, the appended claims are to encompass within their scope all such changes and modifications as are within the true spirit and scope of this invention. Those skilled in the art will appreciate that, in general, terms used herein are generally considered to be "open" terms (e.g., the term "comprising" should be interpreted as "including but not limited to," the term "having" should be interpreted as "having at least," the term "comprising" should be interpreted as "including but not limited to," etc.).

Claims

1. A microfluidic cartridge, comprising:

a molded polymer bonded to the planar surface,

wherein the molded polymer comprises one or more openings for connection to a fluid volume,

and wherein the molded polymer comprises patterns having different heights in different regions, thereby creating regions of different open fluid volumes in the microfluidic cartridge so as to substantially reduce flow resistance.

2. The microfluidic cartridge of claim 1, wherein the planar surface further comprises one or more electrodes.

3. The microfluidic cartridge of claim 1, wherein the one or more openings provide a gas and/or fluid connection.

4. The microfluidic cartridge of claim 1, wherein the molded polymer is an organic molded polymer.

5. The microfluidic cartridge of claim 1, wherein the planar surface comprises a glass surface.

6. The microfluidic cartridge of claim 1, wherein the one or more openings are adapted to introduce fluid into the cartridge without contacting a connection instrument.

7. A method of making a microfluidic cartridge, the method comprising:

(i) The molded polymer was prepared by:

(a) Placing a patterned microfabricated chip into a mold, wherein the microfabricated chip comprises patterns having different heights in different regions; and

(b) Filling the mold with a material in liquid form and/or other shape conforming form to form a molded polymer having patterns with different heights in different areas; and

(ii) The molded polymer is bonded to a planar surface such that the patterns having different heights in different regions create regions of different open fluid volumes in the microfluidic cartridge so as to substantially reduce flow resistance.

8. The method of claim 7, wherein the material is an organic polymer.

9. The method of claim 7, wherein the material is thermally cured and/or time cured.

10. The method of claim 7, wherein the patterned microfabricated chip is fabricated from a silicon substrate.